argenx Meets Phase III Endpoint With Efgartigimod in Autoimmune Myositis

argenx has reported positive Phase III results from the ALKIVIA study, showing that VYVGART® Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) improved disease activity in patients with autoimmune myositis. The study met its primary endpoint in the combined immune-mediated necrotizing myopathy (IMNM) and dermatomyositis (DM) population, demonstrating a 15.4-point greater improvement in mean Total Improvement Score (TIS) at Week 52 compared with placebo (48.0 versus 32.6; p=0.0011). The findings also showed statistically significant improvement in the IMNM subgroup an important development for a disease with no currently approved targeted therapies.

ALKIVIA Meets Primary and Key Secondary Endpoints

ALKIVIA was a global, randomized, double-blind, placebo-controlled, operationally seamless Phase 2/3 study evaluating subcutaneous efgartigimod in patients with IMNM, DM, and polymyositis (PM). The study randomized 265 patients with active disease receiving background treatment. Following analysis of the Phase 2 portion after the first 89 patients completed the study, the Phase 3 portion included 175 treated patients.

Participants received weekly subcutaneous injections of efgartigimod PH20 or matched placebo in a 1:1 ratio. A protocol-mandated corticosteroid taper was implemented throughout Phase 3, and the primary endpoint was mean TIS at Week 52. Prespecified analyses evaluated the combined IMNM and DM population as well as individual disease subtypes.

The study also met its key secondary endpoints in the combined population, including response rate, time to response, muscle strength, and disease activity, extending the primary outcome beyond overall improvement to specific measures of clinical response.

IMNM Shows Statistically Significant Improvement

Patients with IMNM receiving efgartigimod achieved a 14.8-point greater improvement in mean TIS at Week 52 compared with placebo (45.1 versus 30.2; p=0.0048)

Key findings in the IMNM cohort included:

• Clinical Response: A 22.0 percentage-point difference in the proportion of patients achieving TIS , with efgartigimod-treated patients twice as likely to maintain this response through Week 52.
• Muscle Strength: A 5.4-point greater improvement in Manual Muscle Testing-8 (MMT-8) score compared with placebo.
• Muscle Injury Biomarkers: Creatine kinase (CK) levels declined rapidly and remained lower through Week 52, showing a 43.5 percentage-point greater reduction from baseline and a 0.9-grade greater reduction in CK grade versus placebo.
• Disease Activity: Greater improvements in disease activity reported by both patients and physicians using Patient Global Assessment (PGA) and Physician Global Assessment (MDGA).

The sustained reduction in CK a key biomarker of active muscle injury—provides complementary objective evidence supporting the observed improvements in muscle strength and overall clinical response.

DM Shows Favourable Numerical Improvements

In the DM subgroup, efgartigimod demonstrated a 14.5-point greater improvement in mean TIS at Week 52 compared with placebo (51.5 versus 37.0). However, the difference did not reach statistical significance (p =0.1093) with the smaller subgroup size identified as a key contributing factor.

Additional findings in the DM subgroup included:

• A 27.2 percentage-point difference in the proportion achieving TIS, with separation from placebo evident from Week 4 and maintained through Week 52.
• A 5.6-point greater improvement in skin disease activity, measured via the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI).
• Greater improvements reported across both patient and physician assessments of overall disease activity.

While these data show positive numerical trends across muscle and skin outcomes, the non-significant TIS result indicates that efficacy in DM requires further evaluation.

Safety and Regulatory Development

Efgartigimod was generally well tolerated in ALKIVIA, displaying a safety profile consistent with prior trials and established clinical data. Detailed adverse-event frequencies and treatment discontinuation rates were not disclosed in the preliminary reporting.

Based on these results, argenx plans to submit a Supplemental Biologics License Application (sBLA) to the U.S. FDA for efgartigimod in IMNM by the end of 2026. The program is supported by FDA Breakthrough Therapy Designation.

Clinical Interpretation

ALKIVIA provides key Phase III evidence supporting FcRn inhibition as a therapeutic approach in autoimmune myositis. Statistically significant improvements in the primary endpoint and IMNM subgroup backed by consistent gains in muscle strength, global assessments, and biomarker reduction solidify the rationale for efgartigimod in IMNM.

The background corticosteroid taper provides critical real-world context, confirming efficacy even as steroid dosing was reduced (though formal steroid-sparing benefit remains to be formally established). For DM, encouraging numerical trends warrant further study, while planned regulatory filings position IMNM as the primary target for initial approval. Efgartigimod remains investigational for autoimmune myositis.

Reference

argenx Presents Phase 3 ALKIVIA Data at ACR Convergence 2026 Showing Rapid and Sustained Improvement with Efgartigimod in Autoimmune Myositis, argenx, 07 November 2026

A Study to Investigate the Efficacy and Safety of Efgartigimod PH20 SC in Adult Participants with Active Idiopathic Inflammatory Myopathy. (ALKIVIA), ClinicalTrials.gov ID NCT05523167